PDF(Pubmed)
Abstract：
The choroid plexus is an important blood barrier that secretes cerebrospinal fluid, which essential for embryonic brain development and adult brain homeostasis. The OTX2 homeoprotein is a transcription factor that is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative functional roles for OTX2 in adult choroid plexus function, including cell signaling and adhesion, and show that OTX2 regulates the expression of factors that are secreted into the cerebrospinal fluid, notably transthyretin. We also show that Otx2 expression impacts choroid plexus immune and stress responses, and affects splicing, leading to changes in the mRNA isoforms of proteins that are implicated in the oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell-autonomous target regions, such as the visual cortex and subventricular zone, we identify putative targets that are involved in cell adhesion, chromatin structure, and RNA processing. Thus, OTX2 retains important roles for regulating choroid plexus function and brain homeostasis throughout life.
摘要：
脉络丛是分泌脑脊液的重要血液屏障,这对胚胎大脑发育和成人大脑稳态至关重要。OTX2同源异型蛋白是一种对脉络丛发育至关重要的转录因子，并在成年脉络丛中保持高表达。通过对组成型和条件性敲除成年小鼠模型的RNA测序分析，我们揭示了OTX2在成人脉络丛功能中的假定功能作用，包括细胞信号和粘附，并显示OTX2调节分泌到脑脊液中的因子的表达，特别是甲状腺素运载蛋白。我们还表明Otx2表达影响脉络丛免疫和应激反应，并影响拼接，导致与氧化应激反应和DNA修复有关的蛋白质mRNA同工型的变化。通过质谱分析脉络丛中的OTX2蛋白质伴侣，在已知的非细胞自治目标区域，比如视觉皮层和脑室下区，我们确定了与细胞粘附有关的假定目标，染色质结构，和RNA加工。因此，OTX2在整个生命过程中对脉络丛功能和脑稳态的调节具有重要作用。
